ABSTRACT
The availability of taxane-based chemotherapy and androgen-receptor-targeted agents (ARTAs) have significantly broadened the therapeutic options for patients with metastatic prostate cancer and may also result in longer patient survival. The therapeutic sequence of ARTAs and taxanes may influence outcome and therefore decisions should be made on an individual basis. This article provides guidance for therapeutic decision-making in daily clinical practice by working out criteria that can be used to support individual therapeutic decisions. The focus is on metastatic castration-naive prostate cancer, oligometastatic disease as well as non-metastatic and metastatic castration-resistant prostate cancer.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Prostatic Neoplasms, Castration-Resistant/therapy , Androgen Antagonists , Hormone Replacement Therapy , Humans , Male , Molecular Targeted Therapy , Prostate-Specific Antigen/blood , Prostatectomy/methods , Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/pathology , Treatment OutcomeABSTRACT
There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naïve stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.
Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Docetaxel/therapeutic use , Prostatic Neoplasms, Castration-Resistant/therapy , Androgen Antagonists/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Docetaxel/administration & dosage , Humans , Male , Neoplasm Metastasis , Prostatic Neoplasms, Castration-Resistant/pathology , Randomized Controlled Trials as Topic , Survival Rate , Treatment OutcomeABSTRACT
In March 2017 the 'Advanced Prostate Cancer Consensus Conference' (APCCC) took place in St. Gallen (Switzerland). The APCCC-panelists are internationally well known experts. With the actual data in mind they discussed treatment options for patients with advanced prostate cancer in order to update the international APCCC-recommendations from the previous meeting in 2015. Recently these consensus recommendations have been published in "European Urology".A group of German experts discussed this year APCCC-votes during the meeting and the recommendations that were concluded from the votes from the German perspective. Reasons for an additional German discussion are country-specific variations that may have influenced the APCCC-votes und recommendations. Due to the concept of the APCCC-meeting the wording of the questions could not always be as necessary.One focus of this year consensus discussion was the treatment of metastatic castration-naive prostate cancer (mCNPC). There are new data which may also influence the therapeutic situation of patients with metastatic castration-resistant prostate cancer (mCRPC). Further points of discussion were the impact of new imaging procedures in the clinical setting as well as the treatment of oligometastatic prostate cancer.
Subject(s)
Neoplasm Metastasis/diagnostic imaging , Orchiectomy , Practice Guidelines as Topic , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Radiotherapy, Adjuvant , Urology/standards , Evidence-Based Medicine , Germany , Humans , Lymph Node Excision , Lymphatic Metastasis/diagnostic imaging , Magnetic Resonance Imaging , Male , Switzerland , Treatment OutcomeABSTRACT
BACKGROUND: At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented. OBJECTIVES: The focus is on the clinical impact of these data. MATERIALS AND METHODS: A group of German experts in the field of urogenital-oncologic expertise discussed the clinical impact with respect to the current data. RESULTS: The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC. CONCLUSIONS: Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20 mg/m2 cabazitaxel.
Subject(s)
Neoplasms, Second Primary/pathology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Taxoids/therapeutic use , Docetaxel , Humans , Male , Neoplasms, Second Primary/drug therapyABSTRACT
The target of focal therapy (FT) in prostate cancer (PC) is partial treatment of the prostate aiming at preserving surrounding anatomical structures. The intention is to minimize typical side effects of radical treatment options combined with local tumor control. Numerous established and new technologies are used. Results of published studies showed a good safety profile, few side effects and good preservation of functional results. Oncologic long-term data are lacking so far. Photodynamic therapy (PDT) is the only technology that has been studied in a published prospective randomized trial. The FT is challenged by the multifocality of PC; therefore, the quality of prostate biopsy, histopathological assessment as well as imaging are of paramount importance. Multiparametric magnetic resonance imaging (MRI) has gained increasing importance. The FT is experimental and should only be offered within clinical trials.
Subject(s)
Prostatic Neoplasms/therapy , Biopsy , Brachytherapy , Cryotherapy , Disease Progression , Endosonography , High-Intensity Focused Ultrasound Ablation , Humans , Laser Therapy , Magnetic Resonance Imaging , Male , Neoplasm Grading , Neoplasm Staging , Photochemotherapy , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Randomized Controlled Trials as Topic , Sensitivity and SpecificityABSTRACT
BACKGROUND: Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naïve metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival. OBJECTIVE: This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. MATERIALS AND METHODS: A German group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. RESULTS: In the current treatment of hormone-naïve mPC, a beneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with a high metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response <12 months, tumor-associated complaints), first-line chemotherapy is indicated. After docetaxel failure, continuous treatment with cabazitaxel shows superior overall survival compared to sustained antihormonal therapy. CONCLUSION: Chemotherapy is firmly established in treating patients with mCRPC. Long-term, it will be important to identify molecular predictors. The authors suggest the early use of chemotherapy in hormone-naïve mPC, but note that the approval in this indication is currently nonexistent. After disease progression, patients should be treated analogous to mCRPC.
Subject(s)
Antineoplastic Agents/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Taxoids/therapeutic use , Androgen Antagonists/therapeutic use , Antineoplastic Agents/adverse effects , Clinical Trials, Phase III as Topic , Docetaxel/adverse effects , Docetaxel/therapeutic use , Early Medical Intervention , Evidence-Based Medicine , Humans , Male , Neoplasm Metastasis , Prostatic Neoplasms/mortality , Prostatic Neoplasms, Castration-Resistant/mortality , Randomized Controlled Trials as Topic , Survival Rate , Taxoids/adverse effectsABSTRACT
Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.
Subject(s)
Ablation Techniques/methods , Electroporation/methods , Prostatic Neoplasms/therapy , Humans , Male , Prostatic Neoplasms/pathology , Treatment OutcomeABSTRACT
BACKGROUND: Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. OBJECTIVES: Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. MATERIALS AND METHODS: A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). RESULTS: Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. DISCUSSION: Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). CONCLUSIONS: There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/instrumentation , Magnetic Resonance Imaging/instrumentation , Multimodal Imaging/instrumentation , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Equipment Design , Equipment Failure Analysis , Humans , Male , Prostatic Neoplasms/diagnostic imaging , Reproducibility of Results , Sensitivity and Specificity , Technology Assessment, BiomedicalABSTRACT
BACKGROUND: The rising incidence of renal cell carcinoma, its more frequent early detection (stage T1a) and the increasing prevalence of chronic renal failure with higher morbidity and shorter life expectancy underscore the need for multimodal focal nephron-sparing therapy. DISCUSSION: During the past decade, the gold standard shifted from radical to partial nephrectomy. Depending on the surgeon's experience, the patient's constitution and the tumor's location, the intervention can be performed laparoscopically with the corresponding advantages of lower invasiveness. A treatment alternative can be advantageous for selected patients with high morbidity and/or an increased risk of complications associated with anesthesia or surgery. Corresponding risk stratification necessitates previous confirmation of the small renal mass (cT1a) by histological examination of biopsy samples. Active surveillance represents a controlled delay in the initiation of treatment. RESULTS: Percutaneous radiofrequency ablation (RFA) and laparoscopic cryoablation are currently the most common treatment alternatives, although there are limitations particularly for renal tumors located centrally near the hilum. More recent ablation procedures such as high intensity focused ultrasound (HIFU), irreversible electroporation, microwave ablation, percutaneous stereotactic ablative radiotherapy and high-dose brachytherapy have high potential in some cases but are currently regarded as experimental for the treatment of renal cell carcinoma.
Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Minimally Invasive Surgical Procedures/methods , Organ Sparing Treatments/methods , Carcinoma, Renal Cell/pathology , Catheter Ablation , Cryosurgery , Humans , Kidney Neoplasms/pathology , Laparoscopy , Neoplasm Staging , Nephrectomy , Watchful WaitingABSTRACT
In March 2015, the first Advanced Prostate Cancer Consensus Conference (APCC) took place in St. Gallen. 41 experts from 17 countries reviewed important areas of controversy in advanced hormone-naive and castration-resistant prostate cancer and gave therapy recommendations. These results have been recently published in "Annals of Oncology". While most of the recommendations from St. Gallen are comprehensible, some of them need to be further discussed. Therefore, we as a German expert panel will critically debate the St. Gallen recommendations. For metastatic hormone-naive prostate cancer, continuous androgen deprivation remains the standard. There is no evidence for superiority of primary maximal androgen deprivation. Patients suitable for chemotherapy, especially in the presence of high tumour burden, should receive androgen deprivation plus taxanes upfront. In metastatic castration resistant prostate cancer, novel hormonal agents like abiraterone or enzalutamid should be the treatment of choice in the majority of patients. Taxanes should be used first-line in patients with unfavourable prognostic markers. Radium-223 is an option in symptomatic patients with bone metastases. There is first evidence that second-line hormonal treatment after first-line failure of a novel endocrine agent has a high failure rate. Cabazitaxel should be part of the treatment sequence in patients with a good performance status. Baseline staging for castration-resistant prostate cancer should include CT-abdomen/-chest and bone scan. Radiographic monitoring should be performed 2 to 3 times a year. Determination of PSA and ALP is to take place every 2 to 4 months.
Subject(s)
Androgen Antagonists/administration & dosage , Practice Guidelines as Topic , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Taxoids/administration & dosage , Urology/standards , Antineoplastic Agents/administration & dosage , Evidence-Based Medicine , Germany , Humans , Male , Neoplasm Metastasis , Treatment OutcomeABSTRACT
BACKGROUND: Antihormonal and cytotoxic therapy options are available for the therapy of metastasized prostate cancer (mPC). Because no comparative studies are available, especially for castration-resistant prostate cancer (mCRCP), it remains unclear which patients will profit best from which therapy. OBJECTIVES: Previous data on the sequence of the various therapy options show that correct selection of the first line therapy for mCRPC can have an influence on the prognosis of the patient. In this position paper the various therapy options are critically illustrated and the clinical and pathohistological criteria for selection of the first line therapy of mCRPC are discussed. RESULTS: Molecular markers are an important aid for future patient selection and individualized therapy for optimal use of the available forms of therapy.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma/drug therapy , Carcinoma/secondary , Medical Oncology/standards , Practice Guidelines as Topic , Prostatic Neoplasms, Castration-Resistant/drug therapy , Carcinoma/diagnosis , Drug Therapy/standards , Germany , Humans , Male , Prostatic Neoplasms, Castration-Resistant/diagnosisABSTRACT
BACKGROUND: Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy (FT) with its postulated features, especially the absence of a thermal ablative effect. Thus far, there is no adequate tumor-entity-specific proof of its effectiveness, and its clinical application has hitherto been confined to very small patient cohorts. This also holds true for prostate cancer (PCA). Nevertheless, it is now being increasingly applied outside clinical trials-to a certain extent due to active advertising in the lay press. AIM OF THE STUDY: In this study, current discrepancies between the clinical application and study situation and the approval and market implementation of the procedure are described. The media portrayal of IRE is discussed from different perspectives, particularly with reference to the FT of PCA. This is followed by a final clinical assessment of IRE using the NanoKnife® system. DISCUSSION: Strict requirements govern new drug approvals. According to the German Drug Act (AMG), evidence of additional benefit over existing therapy must be provided through comparative clinical trials. For medicotechnical treatment procedures, on the other hand, such trial-based proof is not required according to the Medical Devices Act (MPG). The use of IRE even outside clinical trials has been actively promoted since the NanoKnife® system was put on the market. This has led to an increase in the number of uncontrolled IRE treatments of PCA in the last 2 years. The patients have to cover the high treatment costs themselves in these cases. If articles in the lay press advertise the procedure with promising but unverified contents, false hopes are raised in those concerned. This is disastrous if it delays the use of truly effective treatment options. CONCLUSION: IRE basically still has high potential for the treatment of malignancies; however, whether it can really be used for FT remains unclear due to the lack of data. This also holds true for the treatment of PCA. Only carefully conducted scientific research studies can clarify the unresolved issues regarding IRE of PCA. The urgently needed development of universally valid treatment standards for IRE is unnecessarily hampered by the flow commercially driven patients.
Subject(s)
Ablation Techniques/methods , Electroporation/methods , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Evidence-Based Medicine , Humans , Male , Treatment OutcomeABSTRACT
Faced with the dilemma of choosing between the extremes of standard whole gland therapy and active surveillance, those affected by prostate cancer have recently been on the lookout for less invasive alternatives. Particularly the question of whether it would be possible in low risk cancer to treat only the tumour itself while sparing the organ has long been considered. This article discusses the pros and cons of focal treatment and elucidates the latest innovative technologies. High overtreatment rates in low-risk patients submitted to standard therapy and considerable technological advances in diagnosis (particularly multiparametric MRI) and therapy are regarded by the authors as key arguments for abandoning complete tumour eradication with its side effects in favour of sufficient local cancer control by focal treatment with better preserved quality of life in suitable cases.
Subject(s)
Prostatic Neoplasms/therapy , Biopsy , Disease Progression , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Humans , Image Enhancement/methods , Imaging, Three-Dimensional/methods , Male , Medical Overuse , Neoplasm Grading , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/therapy , Predictive Value of Tests , Prognosis , Prostate/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Treatment OutcomeABSTRACT
Transrectal ultrasound-guided prostate biopsy is considered the gold standard in the primary investigation of a suspicious prostate-related finding. The procedure can be carried out with ten probes or more on the lateral side of the prostate, after administering antibiotic prophylaxis and applying local anesthesia. The indication for a biopsy depends on the results of the digitorectal examination, on the serum prostate-specific antigen level, on the individual patient's wish and on his comorbidities. Whether multiparametric imaging should be used before or during the course of a primary or repeated biopsy in order to identify suspicious prostate lesions is the subject of current investigations. Extended biopsy protocols require further clinical investigations before they can become the new standard in the diagnostic work-up. This review delivers an update on the indication for, and technique of, prostate biopsies.
Subject(s)
Early Detection of Cancer/trends , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Endoscopic Ultrasound-Guided Fine Needle Aspiration/trends , Prostatic Neoplasms/pathology , Watchful Waiting/methods , Early Detection of Cancer/methods , Forecasting , Humans , Male , Prognosis , Prostatic Neoplasms/classification , Risk Assessment/methodsABSTRACT
BACKGROUND: In localized low-risk prostate cancer (PCa), there is a therapeutic dilemma between possible overtreatment by one of the standard therapies and potentially insufficient cancer control by active surveillance (AS). Focal therapy (FT) provides an alternative therapeutic option as it aims to preserve the organ and to eliminate the cancer focus at the same time. METHODS: In this article the current state of FT for localized low-risk prostate carcinoma in Germany is described. In addition, criteria that should be used to select patients for FT are proposed. RESULTS: Currently, the effectiveness of FT is under evaluation by two multicenter, prospective studies in Germany: TOOKAD and HEMI. However, localized low-risk prostate carcinoma remains a diagnostic challenge: Multiparametric MRI as well as histopathological second opinion are considered mandatory in addition to transrectal biospy. CONCLUSION: The oncological outcome of both the TOOKAD and HEMI study will be crucial for any form of FT for prostate carcinoma in Germany in the future. However, there is a remarkably high acceptance of FT among patients.
Subject(s)
Minimally Invasive Surgical Procedures/methods , Organ Sparing Treatments/methods , Prostatectomy/methods , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Radiotherapy, Conformal/methods , Evidence-Based Medicine , Germany , Humans , Male , Prognosis , Risk Assessment/methods , Treatment Outcome , Watchful Waiting/methodsABSTRACT
INTRODUCTION: Patients with low-risk prostate cancer (PCa) face the difficult decision between a potential overtreatment by one of the standard therapies and active surveillance (AS) with the potential insecurity regarding cancer control. A focal therapy (FT) implies a treatment of the tumor within the prostate only. METHODS: This review evaluates the current literature and expert opinion of different therapies suited for FT as well as concepts for prostate imaging, biopsy and histopathological evaluation. RESULTS: Currently there is a lack of multicenter, randomized, prospective data on the effectiveness of FT. Nonetheless, the published data indicate a sufficient tumor control with a favorable side effect profile. There are still flaws in the diagnostics with regard to tumor detection and histological evaluation. Multicenter studies are currently recruiting worldwide which will provide new data with a higher level of evidence. CONCLUSION: At present, the effectiveness of FT should not be compared directly to standard radical therapies and FT should only be performed within studies. In cases of cancer progression after FT a salvage treatment should still be possible.
Subject(s)
Ablation Techniques/trends , Prostatectomy/trends , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Salvage Therapy/trends , Humans , Male , Treatment OutcomeSubject(s)
Adenocarcinoma/diagnosis , Glutathione S-Transferase pi/genetics , Promoter Regions, Genetic/genetics , Prostatic Neoplasms/diagnosis , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Biopsy , Humans , Male , Methylation , Prognosis , Prostate/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathologyABSTRACT
Positron emission tomography (PET) with the use of ((18)F)2-fluoro-D: -2-desoxyglucose (FDG) has been investigated to be a highly sensitive and specific imaging modality in the diagnostic of primary and recurrent tumors and in the control of therapies in numerous non-urologic cancers. The aim of this review is to validate the significance of PET as a diagnostic tool in malignant urological tumors of the small pelvis. A systematic review of the current literature concerning the role of PET for malignant prostate, testicular and bladder tumors was carried out. The data indicate no additional role for PET in comparison with conventional imaging in tumor detection and local staging for prostate, bladder or testicular cancer. Tumor recurrence in prostate cancer seems to be more effectively identified with acetate and choline than with FDG, but this effect is more pronounced with higher PSA values. The value of PET in the identification of metastatic disease in either tumor entity can not be finally outlined as the clinical data are partly missing, controversial or in the process of evaluation. FDG-PET can be regarded as accepted imaging modality in the restaging of seminomatous germ cell tumors after chemotherapy.